Research advances in the epidemiology and mechanism of the association between metabolic dysfunction-associated fatty liver disease and pancreatic cancer

Feng ZHANG; Yifan ZHANG; Yulan LIU

doi:10.12449/JCH251026

Volume 41 Issue 10

Oct. 2025

Turn off MathJax

Article Contents

Article Navigation > Journal of Clinical Hepatology > 2025 > 41(10): 2136-2140

PDF( 632 KB)

Research advances in the epidemiology and mechanism of the association between metabolic dysfunction-associated fatty liver disease and pancreatic cancer

DOI: 10.12449/JCH251026

Feng ZHANG^{1, 2},
Yifan ZHANG^{1, 2},
Yulan LIU^{1, 2
,
,
,}

1.
Department of Gastroenterology, Peking University People’s Hospital，Beijing 100044，China
2.
Clinical Center of Immune-mediated Digestive Diseases, Peking University People’s Hospital，Beijing 100044，China

Research funding:

Beijing Natural Science Foundation (7242156);

Key Research Project of Capital Health Development Scientific Research Special Program (CFH2024-1-4081);

General Project of National Natural Science Foundation of China (82100579);

Peking University People’s Hospital Scientific Research Development Funds (RDX2022-07)

More Information

Corresponding author: LIU Yulan， liuyulan@pkuph.edu.cn （ORCID： 0000-0001-5026-7828）
Received Date: 2025-03-27
Accepted Date: 2025-04-21
Published Date: 2025-10-25

Abstract

Abstract

Metabolic dysfunction-associated fatty liver disease （MAFLD） has a relatively high prevalence rate around the world and is closely associated with the development of various extrahepatic malignancies， among which pancreatic cancer exhibits the highest mortality rate. However， the underlying mechanism between MAFLD and pancreatic cancer remains unclear. This article systematically introduces the latest epidemiological evidence of the association between MAFLD and pancreatic cancer， reviews the research advances in pathogenesis， and evaluates the impact of MAFLD severity and high-risk factors （such as nonalcoholic fatty pancreatic disease and intraductal papillary mucinous neoplasm） on the risk of pancreatic cancer. This article points out that insulin resistance， adipokines， and gut dysbiosis may be the key mechanisms of MAFLD promoting the onset of pancreatic cancer， and it also highlights the presence of heterogeneity in current studies. Large-scale prospective cohort studies are needed in the future to further validate the causal relationship and explore more effective strategies for risk stratification.
- Metabolic Dysfunction-Associated Fatty Liver Disease,
- Pancreatic Neoplasms,
- Risk Factors,
- Pathologic Processes

FullText(HTML)

References(32)

References

[1]	YOUNOSSI ZM, GOLABI P, PAIK JM, et al. The global epidemiology of nonalcoholic fatty liver disease(NAFLD) and nonalcoholic steatohepatitis(NASH): A systematic review[J]. Hepatology, 2023, 77( 4): 1335- 1347. DOI: 10.1097/HEP.0000000000000004.
[2]	CHEN L, FAN JG. The evolution of international definitions of fatty liver disease and insights into the working definition and features of the 2024 Chinese guideline[J]. Chin J Clin Med, 2025, 32( 3): 321- 326. DOI: 10.12025/j.issn.1008-6358.2025.20250107. 陈立, 范建高. 从国际脂肪性肝病定义的变迁看2024版中国指南的工作定义与特色[J]. 中国临床医学, 2025, 32( 3): 321- 326. DOI: 10.12025/j.issn.1008-6358.2025.20250107.
[3]	PIPITONE RM, CICCIOLI C, INFANTINO G, et al. MAFLD: A multisystem disease[J]. Ther Adv Endocrinol Metab, 2023, 14: 20420188221145549. DOI: 10.1177/20420188221145549.
[4]	MIZRAHI JD, SURANA R, VALLE JW, et al. Pancreatic cancer[J]. Lancet, 2020, 395( 10242): 2008- 2020. DOI: 10.1016/S0140-6736(20)30974-0.
[5]	TANASE DM, GOSAV EM, COSTEA CF, et al. The intricate relationship between type 2 diabetes mellitus(T2DM), insulin resistance(IR), and nonalcoholic fatty liver disease(NAFLD)[J]. J Diabetes Res, 2020, 2020: 3920196. DOI: 10.1155/2020/3920196.
[6]	CHEN ZB, HUANG LY, WANG BY, et al. Research advances in the association between metabolic associated fatty liver and type 2 diabetes mellitus and the mechanism of comorbidity[J]. J Clin Hepatol, 2023, 39( 10): 2454- 2459. DOI: 10.3969/j.issn.1001-5256.2023.10.025. 陈兆斌, 黄丽媛, 王炳元, 等. 代谢相关脂肪性肝病与2型糖尿病的关系及共病机制研究进展[J]. 临床肝胆病杂志, 2023, 39( 10): 2454- 2459. DOI: 10.3969/j.issn.1001-5256.2023.10.025.
[7]	SIMON TG, ROELSTRAETE B, SHARMA R, et al. Cancer risk in patients with biopsy-confirmed nonalcoholic fatty liver disease: A population-based cohort study[J]. Hepatology, 2021, 74( 5): 2410- 2423. DOI: 10.1002/hep.31845.
[8]	VUJASINOVIC M, EBRAHIMI F, ROELSTRAETE B, et al. Metabolic dysfunction-associated steatotic liver disease and pancreatic disease-a population-based nationwide cohort and sibling-controlled study[J]. United European Gastroenterol J, 2025, 13( 2): 247- 256. DOI: 10.1002/ueg2.12761.
[9]	LIU ZQ, LIN CQ, SUO C, et al. Metabolic dysfunction-associated fatty liver disease and the risk of 24 specific cancers[J]. Metabolism, 2022, 127: 154955. DOI: 10.1016/j.metabol.2021.154955.
[10]	POWELL EE, ROCHE S, SARRAF B, et al. Australians with metabolic dysfunction-associated steatotic liver disease have a twofold increase in the incidence of cancer[J]. JGH Open, 2024, 8( 7): e70000. DOI: 10.1002/jgh3.70000.
[11]	ZHOU BG, JIANG X, SHE Q, et al. Association of MASLD with the risk of extrahepatic cancers: A systematic review and meta-analysis of 18 cohort studies[J]. Eur J Clin Invest, 2024, 54( 11): e14276. DOI: 10.1111/eci.14276.
[12]	ZHANG Y, ZHOU BG, ZHAN JD, et al. Association between metabolic dysfunction-associated steatotic liver disease and risk of incident pancreatic cancer: A systematic review and meta-analysis of cohort studies[J]. Front Oncol, 2024, 14: 1366195. DOI: 10.3389/fonc.2024.1366195.
[13]	KIM GA, LEE HC, CHOE J, et al. Association between non-alcoholic fatty liver disease and cancer incidence rate[J]. J Hepatol, 2018, 68( 1): 140- 146. DOI: 10.1016/j.jhep.2017.09.012.
[14]	YUAN XJ, WANG XM, WU SL, et al. Associations between metabolic dysfunction-associated fatty liver disease and extrahepatic cancers: A cohort in China[J]. Hepatobiliary Surg Nutr, 2023, 12( 5): 671- 681. DOI: 10.21037/hbsn-21-546.
[15]	WANG ZY, ZHAO XY, CHEN SH, et al. Associations between nonalcoholic fatty liver disease and cancers in a large cohort in China[J]. Clin Gastroenterol Hepatol, 2021, 19( 4): 788- 796. DOI: 10.1016/j.cgh.2020.05.009.
[16]	MCHENRY S, ZONG XY, SHI MY, et al. Risk of nonalcoholic fatty liver disease and associations with gastrointestinal cancers[J]. Hepatol Commun, 2022, 6( 12): 3299- 3310. DOI: 10.1002/hep4.2073.
[17]	SUN LM, LIN MC, LIN CL, et al. Nonalcoholic cirrhosis increased risk of digestive tract malignancies: A population-based cohort study[J]. Medicine(Baltimore), 2015, 94( 49): e2080. DOI: 10.1097/MD.0000000000002080.
[18]	HORI M, TAKAHASHI M, HIRAOKA N, et al. Association of pancreatic Fatty infiltration with pancreatic ductal adenocarcinoma[J]. Clin Transl Gastroenterol, 2014, 5( 3): e53. DOI: 10.1038/ctg.2014.5.
[19]	ZHANG CL, WANG JJ, LI JN, et al. Nonalcoholic fatty pancreas disease: An emerging clinical challenge[J]. World J Clin Cases, 2021, 9( 23): 6624- 6638. DOI: 10.12998/wjcc.v9.i23.6624.
[20]	LEE JS, KIM SH, JUN DW, et al. Clinical implications of fatty pancreas: Correlations between fatty pancreas and metabolic syndrome[J]. World J Gastroenterol, 2009, 15( 15): 1869- 1875. DOI: 10.3748/wjg.15.1869.
[21]	CHOI CW, KIM Y, KIM JE, et al. Enhancement of lipid content and inflammatory cytokine secretion in SZ95 sebocytes by palmitic acid suggests a potential link between free fatty acids and acne aggravation[J]. Exp Dermatol, 2019, 28( 2): 207- 210. DOI: 10.1111/exd.13855.
[22]	SUN H, SUN ZL, VARGHESE Z, et al. Nonesterified free fatty acids enhance the inflammatory response in renal tubules by inducing extracellular ATP release[J]. Am J Physiol Renal Physiol, 2020, 319( 2): F292- F303. DOI: 10.1152/ajprenal.00098.2020.
[23]	SBEIT W, GREENER T, KADAH A, et al. Pancreatobiliary manifestations of nonalcoholic fatty liver disease: A retrospective case-control multicenter study[J]. Eur J Gastroenterol Hepatol, 2021, 33( 5): 722- 726. DOI: 10.1097/MEG.0000000000001780.
[24]	REZENDE AQM, GESTIC MA, UTRINI MP, et al. Is there a link between non-alcoholic fatty liver disease aspects and pancreatic cancer? Results of a case-matched study[J]. Rev Col Bras Cir, 2021, 48: e20202913. DOI: 10.1590/0100-6991e-20202913.
[25]	TORRES C, MANCINELLI G, CORDOBA-CHACON J, et al. p110γ deficiency protects against pancreatic carcinogenesis yet predisposes to diet-induced hepatotoxicity[J]. Proc Natl Acad Sci USA, 2019, 116( 29): 14724- 14733. DOI: 10.1073/pnas.1813012116.
[26]	CHANG ML, YANG Z, YANG SS. Roles of adipokines in digestive diseases: Markers of inflammation, metabolic alteration and disease progression[J]. Int J Mol Sci, 2020, 21( 21): 8308. DOI: 10.3390/ijms21218308.
[27]	ZHAO CL, SHANG DF, ZHOU C, et al. Mechanisms of lipid metabolism mediated by hepatokines and adipokines in nonalcoholic fatty liver disease[J]. J Clin Hepatol, 2023, 39( 1): 168- 174. DOI: 10.3969/j.issn.1001-5256.2023.01.026. 赵晨露, 尚东方, 周铖, 等. 肝因子和脂肪因子介导的脂代谢在非酒精性脂肪性肝病中的作用机制[J]. 临床肝胆病杂志, 2023, 39( 1): 168- 174. DOI: 10.3969/j.issn.1001-5256.2023.01.026.
[28]	TILG H, ADOLPH TE, MOSCHEN AR. Multiple parallel hits hypothesis in nonalcoholic fatty liver disease: Revisited after a decade[J]. Hepatology, 2021, 73( 2): 833- 842. DOI: 10.1002/hep.31518.
[29]	BRUNETTO E, DE MONTE L, BALZANO G, et al. The IL-1/IL-1 receptor axis and tumor cell released inflammasome adaptor ASC are key regulators of TSLP secretion by cancer associated fibroblasts in pancreatic cancer[J]. J Immunother Cancer, 2019, 7( 1): 45. DOI: 10.1186/s40425-019-0521-4.
[30]	OHKUSA T, NISHIKAWA Y, SATO N. Gastrointestinal disorders and intestinal bacteria: Advances in research and applications in therapy[J]. Front Med(Lausanne), 2023, 9: 935676. DOI: 10.3389/fmed.2022.935676.
[31]	LI GQ, LIU LW, LU TQ, et al. Gut microbiota aggravates neutrophil extracellular traps-induced pancreatic injury in hypertriglyceridemic pancreatitis[J]. Nat Commun, 2023, 14( 1): 6179. DOI: 10.1038/s41467-023-41950-y.
[32]	TABRIZI E, TABRIZI FPF, KHALED GM, et al. Unraveling the gut microbiome’s contribution to pancreatic ductal adenocarcinoma: Mechanistic insights and therapeutic perspectives[J]. Front Immunol, 2024, 15: 1434771. DOI: 10.3389/fimmu.2024.1434771.

Relative Articles

Supplements(0)

Cited By

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Get Citation

PDF

XML

Article Metrics

Article views (42) PDF downloads(10)

Research advances in the epidemiology and mechanism of the association between metabolic dysfunction-associated fatty liver disease and pancreatic cancer

DOI: 10.12449/JCH251026

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Research advances in the epidemiology and mechanism of the association between metabolic dysfunction-associated fatty liver disease and pancreatic cancer

DOI: 10.12449/JCH251026

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content